Alpha-1-antitrypsin (AAT) is the major proteinase inhibitor in human sera. The most common form of the glycoprotein (i.e., the homozygote MM phenotype), as well as the homozygote ZZ phenotype which is associated with chronic obstructive lung disease, have been purified using classical chromatographic procedures. Spectral studies will be used to study both native and chemically modified AAT from each of these variant forms. In addition, the analysis of specific peptide and glycopeptide regions of these proteins will be made, and additional investigations will be undertaken on AAT isolated directly from the livers of deficient individuals. The data obtained should provide new information on the boisynthesis of AAT, and on its transport both into and out of cells, with particular reference to deposition of AAT in the livers of ZZ individuals. The information which we derive should have general applicability to other glycoproteins as well. In an additional study, a series of experiments is planned on the physiological action of AAT, with particular reference to the role of the unusually reactive disulfide bond. Finally, elastase and chymotrypsin-like proteases will be purified from leukocytes and their interaction with AAT and other protease inhibitors studied.